Schizophrenia and memory impairment: evidence for a neurocognitive subtype
Introduction
Schizophrenia is an enigmatic condition that has puzzled clinicians and researchers for over a century. It has been suggested that the illness is a heterogeneous collection of syndromes rather than a single disease entity (Andreasen et al., 1995, Basso et al., 1998, Bellack, 1994, Johnstone and Frith, 1996). This heterogeneity takes the form of extensive variability in symptom expression, course and outcome, cognitive brain function and biological findings.
One strategy for addressing illness heterogeneity is to identify more homogeneous groups of patients within the schizophrenia patient population. The method most commonly employed involves the use of symptoms to create typologies and subclassifications (e.g. Carpenter et al., 1985, Crow, 1980, American Psychiatric Association, 1994, Morrison et al., 1990, Nicholson and Neufeld, 1993, Silverstein et al., 1990). Patients have been classified into positive and negative, type I and type II, paranoid and non-paranoid subtypes among others, but the stability and validity of these distinctions remains questionable (see Marneros et al., 1992, Zuckerman, 1999). Heinrichs and Awad (1993) argued that subtyping derived from symptom ratings was problematic because the ratings are subjective, fluctuate over time, and may be difficult to understand in terms of neural mechanisms. Moreover, the relation of symptoms and functional outcomes in schizophrenia is weak (Green, 1996). This situation has encouraged a decline of interest in discrete subtyping in favor of dimensional approaches that organize symptoms into clusters with no assumption that these clusters correspond to distinct groups of patients (Liddle and Morris, 1991, Waddington and Morgan, 2001).
To address issues of objectivity and stability and provide an alternative to symptom-based subtyping, researchers have suggested that schizophrenia should be parsed and organized with neuropsychological variables (Goldstein, 1994, Heinrichs, 1993, Heinrichs, 2001). Neurocognitive data are performance-based, more objective than symptom ratings and more strongly related to functional outcome (Green et al. 2000). Additionally, the field of neuropsychology has an extensive knowledge base relating brain to behavior, and this can be exploited in the search for new typologies for schizophrenia.
As a case in point, memory impairment constitutes a significant cognitive defect in many patients with the illness (Aleman et al., 1999, Heinrichs and Zakzanis, 1998, Paulsen et al., 1995). However, no clear pattern linking memory function with symptoms has been established (Desgranges et al., 1998, Kolb and Whishaw, 1996, Ruppin et al., 1996, Squire, 1986). Memory performance has been found to be associated with varied symptom clusters, including negative symptoms (Aleman et al., 1999, Basso et al., 1998, McCreadie et al., 1997, Stirling et al., 1997, Tamlyn et al., 1992), anergia (Goldberg et al., 1989), positive symptoms (Brébion et al., 1997), and formal thought disorder (Docherty et al., 1996, Tamlyn et al., 1992). Conversely, memory function has also been found to be independent of symptoms (Addington et al., 1991, Harvey et al., 1986) or to be characterized by a disconnected pattern of relations with symptoms (Schröder et al., 1996).
Memory processes have been associated with the prefrontal cortex (Barch et al., 2002, Tulving et al., 1994a) and the medial regions of the temporal lobes (Heckers et al., 1998, Kolb and Whishaw, 1996, Tulving et al., 1994b). The medial temporal lobe has also been implicated in positive symptom processes (Honer et al., 1994, Ruppin et al., 1996). Yet, medial temporal brain abnormalities are found in only a portion of the schizophrenia patient population (Lawrie and Abukmeil, 1998) and it is clear that not all patients have verbal memory impairment (Heinrichs and Awad, 1993). Therefore, it seems likely that subgroups of patients with normal and abnormal verbal memory function exist. Dimensional single disease-state views dispute this likelihood and hold that all schizophrenia patients are impaired relative to their own pre-illness baselines (see Daniel et al., 1991). However, information on pre-illness functioning is seldom available, making this counter argument hard to test. In contrast, given the availability and non-invasive nature of psychometric techniques, the validity of discrete neurocognitive subtypes is readily evaluated in the diagnosed patient population.
In view of these considerations, we undertook to divide schizophrenia into two subtypes based on verbal memory test performance and to provide a preliminary indication of the validity of this approach for organizing symptomatic and functional aspects of the illness. Our premise was that verbal memory dysfunction reflects a disturbance in fronto-temporal systems and that this disturbance has symptomatic and functional consequences. However, the dysfunction characterizes only a portion of the generic schizophrenia patient population. Therefore, it was hypothesized that memory-impaired patients would be more symptomatic, with lower quality of life, than memory-unimpaired patients.
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Subjects
Fifty-five subjects meeting DSM-III-R criteria for schizophrenia (American Psychiatric Association, 1987) were recruited from local mental health programmes affiliated with the Queen Street Mental Health Center, a large provincial psychiatric facility located in Toronto, Ontario, Canada. The following inclusion criteria were met by all subjects: (a) age between 18 and 65 years, (b) no demonstrable brain disease (i.e. no loss of consciousness and no history of neurological conditions such as
Demographic, illness and cognitive variables
Table 1 presents the demographic, illness, and cognitive characteristics of the patients classified as either memory-impaired or memory-unimpaired. The memory-based groups did not differ significantly on any of the demographic variables. Both groups comprised patients with an average age between 39 and 43 years. Additionally, both subtypes achieved approximately a grade 10 education and had similar socioeconomic backgrounds. The memory-unimpaired group had an equal number of men and women (8
Discussion
This study provides preliminary evidence that subtypes based on the presence or absence of verbal memory impairment exhibit different clinical characteristics in the schizophrenia patient population and may be helpful in organizing some aspects of the heterogeneity of the illness. Differences in symptom expression were found, with the memory-impaired group exhibiting more positive symptoms than the memory-unimpaired group. The associated effect sizes for the five BPRS symptoms that constitute
Acknowledgements
Research reported in this article was supported by the Ontario Mental Health Foundation. An earlier version was presented at the American Psychiatric Association convention, April 2000, in Chicago, Illinois, and at the International Congress of Schizophrenia Research, May 2001, Whistler, B.C., Canada.
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